Immune diseases such as allergic diseases, autoimmune diseases and graft-versus-host diseases (GVHD) are the disease caused by abnormality or incompatibility of the immune system. Among them, patients with some illness of allergic disease tend to increase year by year, and it has been reported that 70% of Japanese people have already affected with some allergic disease. A category of the allergic diseases is broad and includes asthma, atopic dermatitis, pollinosis, food allergy and allergodermia. Many of the patients with allergy are known to develop various allergic diseases sequentially, which is referred to as allergy march. In recent years in Japan, the patients with pollinosiss or pediatric atopic asthma complicated with allergic rhinitis or allergic conjunctivitis have increased markedly. As a reason for this, it has been thought that change of life environment, particularly the change of immunological environment (decrease of bacterial infection, increase of house dust density in an airtight house) in infant in which the immune system is formed may increase the production of IgE antibody. It is evident that narrowly defined allergic diseases such as allergic rhinitis, allergic conjunctivitis and atopic asthma are caused by type I allergic reaction in which the IgE antibody and Th2 cells which induce the production of the antibody are involved. It has been frequently reported that the IgE antibody and the predominant Th2 cells are deeply involved during the stage of occurrence of other various allergic diseases other than them. From the above, it is predicted that depressed production of the IgE antibody which is responsible for the type I allergic reaction and inhibition of Th2 cell differentiation can be promising procedures for therapy of the allergic diseases. For the patients with allergic disease predicted to further increase in the future, a causal therapy by medicaments made based on allergy occurrence mechanisms or a preventive (vaccine) method which reduces the allergy from occurring are thought to be somehow effective. It is necessary to assure high safety profile (low side effect) for remedy.
A humanized anti-IgE antibody (rhuMAb-E25, Genentech Inc.) has been shown to be highly effective in clinical trials with the patients with atopic asthma (see Non-patent literature 1). In an attempt to inhibit the production of an antigen specific IgE antibody using an artificial compound, an immune response of Th1 type was induced in BALB/c mice immunized with a plasmid DNA in which cedar pollen antigen Cry j1 gene had been incorporated. As a result, an IgG2a antibody was produced, and even when the Cry j1 antigen and alum were boosted, the production of IgG1 and IgE antibodies was suppressed (see Non-patent literature 2). When the mouse was immunized with an OVA-IL-12 fusion protein, the immune response of OVA specific Th1 type was induced. Its efficiency was much higher than in the case of being immunized with a mixture solution of OVA and IL-12, and the OVA specific IgG2a antibody was produced (see Non-patent literature 3). This report indicates that the response can be biased to the Th1 type by the immunization with a complex of the antigen and a cytokine inducer and along with it the antigen specific production of the IgE antibody can be suppressed.
To prevent the allergic disease or lead it to cure, it can be an effective procedure to control regulatory cells which suppress the differentiation, proliferation and functions of Th cells and IgE antibody producing B cells. An NKT cell is believed to be one of the regulatory cells which plays an important role in cancer cells, parasites and protozoa, and for eliminating intracellularly infected bacteria such as Listeria and tuberculosis germs (see Non-patent literature 4). It has been demonstrated that the NKT cell is an intermediate TCR cell (TCRint cell) which expresses a T cell receptor (TCR) moderately, and is the cell analogous to an Natural Killer (NK) cell in points of exhibiting a large granular lymphocyte (LGL)-like morphology, constitutively expressing IL-2R β chain on the surface and having perforin granules, but is absolutely different from the NK cell in point of having TCR (see Non-patent literature 5). A Vα14+ NKT cell is one of subsets of the above NKT cells, many of the Vα14+ NKT cells express Vα14Jα281 mRNA and have this as TCR α chain. A Vα24JaQ chain, a human homolog which is homologous to the murine Vα14Ja281 chain is present at 20 to 50% in peripheral blood CD4−/CD8− T cells in healthy donors (see Non-patent literature 6).
α-Galactosyl ceramide which is a ligand compound of these NKT cells induces the cytokine production of both IFN-γ and IL-4. Thus, it has been shown that the NKT cell is the regulatory cell for the differentiation of Th1/Th2 (see Non-patent literature 7). When α-galactosyl ceramide was administered to C57BL/6 mice, the production of IgE antibody induced by DNP-OVA and alum was inhibited. In the same experiment using mice deleting the Vα14-NKT cells, the production of IgE antibody was not inhibited (see Non-patent literature 8). In the experiments in which α-galactosyl ceramide compound was administered to NOD mice, a type I diabetes model, the symptomatic improvement was observed. Thus, the possibility has been suggested that the Vα14-NKT cell augments the immune response via Th2 cells (see Non-patent literature 9). However, the effect obtained by α-galactosyl ceramide compound alone is limited, and further improvement of medicinal efficacy has been required.
Meanwhile, substances of β-galactosyl ceramide and β-glycosyl ceramide are present in vivo, but it has been shown that they have much lower activity compared with immunopotentiation and anti-tumor effects of α-galactosyl ceramide compound (see Non-patent literatures 10 to 12, and Patent document 1).
Additionally, the NKT cell has been known to effectively serve for autoimmune diseases (see Non-Patent literatures 13 to 16). Therefore, if immunosuppressive functions, e.g., the production of IL-10 in the NKT cells can be selectively augmented, it is thought to be effective for the treatment of not only the allergic diseases but also the other immune diseases such as autoimmune diseases and GVHD. However, no ligand which alone can selectively augment the immunosuppressive function of the NKT cell has been known. No liposome has been used for such a purpose.
Patent document 1: JP Hei-1-93562 A, Publication;    Non-patent literature 1: Immunopharmacology, 48:307 (2000);    Non-patent literature 2: Immunology, 99:179 (2000);    Non-patent literature 3: J. Immunol., 158:4137 (1997);    Non-patent literature 4: Clin. Immunol., 28, 1069 (1996);    Non-patent literature 5: J. Immunol., 155, 2972 (1995);    Non-patent literature 6: J. Exp. Med., 182, 1163 (1995);    Non-patent literature 7: Nakayama. T., et al., Int. Arch. Allergy Immunol., 124, 38-42 (2001);    Non-patent literature 8: J. Exp. Med., 190, 783-792, (1999);    Non-patent literature 9: Nat. Med., 7:1052-1056 (2001);    Non-patent literature 10: Biochem. Biophys. Acta, 280, 626 (1972);    Non-patent literature 11: Biochem. Biophys. Acta, 316, 317 (1973);    Non-patent literature 12: Biol. Pharm. Bull., 18, 1487 (1995);    Non-patent literature 13: J. Exp. Med., 186:677 (1997);    Non-patent literature 14: J. Immunol., 166:62 (2001);    Non-patent literature 15: J. Exp. Med., 194:1801 (2001); and    Non-patent literature 16: Nature, 413:531 (2001).